Gas mixing, a process which depends upon the geometry and flow patterns within the pulmonary airways, is critical to ventilation of the alveoli. The long-range objective of this research is to develop a better understanding of gas mixing mechanisms, especially in the conducting airways. The proposed research specifically addresses the possible role of interregional mixing at the high frequency/low tidal volume conditions where mechanical ventilation of critically-ill patients is sometimes conducted. Moreover, the possible existence of an optimal frequency at which gas mixing is maximized will be explored. The bolus-response method is the means by which mixing is to be evaluated: a bolus of an inert gas is injected at the lips during inspiration and its dispersion into surrounding air is determined by monitoring the expired gas fraction. This technique will be employed to measure argon mixing in healthy human subjects over a range of forced oscillatory frequencies of 60 to 1800 breaths per minute (bpm) and tidal volumes from 5 to 50ml. Five subjects whose airway geometry was previously characterized by acoustic reflectance will first be studied during normal breathing with variable breath holding periods. These control experiments will be used to develop data processing methods and to establish baseline values of the argon mixing coefficients. The same subjects will then participate in high frequency experiments in which forced oscillations will be superimposed on breath holding periods ranging from 1 to 4 seconds. By accounting for the baseline values, the mixing coefficient for pure oscillation alone will be determined and correlated with the ventilatory frequency. Complementary studies in physical models will be conducted at the same oscillation frequencies and tidal volumes. Both a single bifurcation and a five-generation symmetric tube network model will be constructed, and terminal flow resistance and compliance will be adjustable in each model so that varying degrees interregional flow can be induced. The magnitude of interregional flow will be characterized by hot film anemometry and corresponding carbon dioxide mixing coefficients will be measured by bolus-response. By correlating the mixing coefficients with oscillation frequency and with degree of interregional flow, it should be possible to determine their interdependency.